1. Field of Invention
The invention relates to cellulose granules and to a process for producing the same and is particularly directed to cellulose granules which are suitable for use as an excipient in tableting, especially by the direct compression method, and to a process for producing the same.
2. Prior Art
Flocked cellulose materials, in the form of subdivided fibers or fiber fragments having varying degrees of fiber characteristics, have found use in the pharmaceutical industry as binders and disintegrants in the making of pharmaceutical tablets. Such materials have found use in the two-stage process known as wet granulation, in which the various ingredients are first blended with a moistening liquid to form a pasty mass which is then sized through a coarse sieve. The wet granules are then dried and, if necessary, broken up again in a hammermill and resized to the desired mesh size of, for example, twenty-five to one hundred (25-100) mesh. The finished granules are then in a condition which permits adequate flow rates in a formulated pharmaceutical preparation from the feed hopper to the tablet dies of a compressing machine.
Another approach to the manufacture of tablets is by the direct compression method, in which the ingredients are merely dry blended by simple admixture and then fed directly to tableting dies. This method offers substantial savings in time and equipment, but an absolute requisite for employment of this process is that all ingredients have a high order of fluidity. It is in this area of direct compression tablet production that previously-available flocked cellulose materials fall down. The previously-available materials fail to fulfill the requisites for compression tablet making to an adequate extent. These requisites are as follows: The material must be free-flowing, it must have binding properties, and it must not stick to punches or dies. These requirements are taken from page fifteen of the text entitled "Tablet Making" by Arthur Little and K. A. Mitchell, Second Edition, The Northern Publishing Co., Ltd., Liverpool, England, 1968. In addition, the tablets produced must disintegrate readily in aqueous or gastric solution.
Microcrystalline cellulose has been the most commercially acceptable such excipient, but there is considerable room for improvement in respect to its cost and its flow and disintegration characteristics. Also, dry-granulated flocked cellulose according to U.S. Pat. No. 4,269,859 has found use as such an excipient but its color, compressibility, and uniformity of performance from batch to batch has left room for considerable improvement.
Thus, since the previously-available cellulose materials do not fill these requisites, it has become desirable to find another form of cellulose which may be employed in the direct compression manufacture of tablets, which is free-flowing and particulate and still able to impart the necessary degree of binding to the tablet ingredients and which, although imparting a certain requisite degree of hardness to the tablet, also permits the formed tablet to disintegrate at an adequate rate in aqueous or gastric solution. The problem is thus to provide a cellulose material of adequate fluidity and a method of transforming existing materials of an intransigent, non-flowing particulate nature into a form which flows readily but without compromising its chemical nature by the addition of foreign matter such as gum or other binding agent.
Such novel form of cellulose and method of producing the same are provided according to the present invention.
Of course, any cellulose material must meet additional requirements if it is to be used in pharmaceutical tableting, for example, all of the usual tests listed for Powdered Cellulose in the National Formulary, Volume XV, page 1219 and, if the end product is to be ingested by a human, then cellulose material must meet additional requirements as set forth in the Food Chemical Codex, Third Edition, pages 80-81. Such additional requirements are of course well known to one skilled in the art and, it goes without saying, form no part of the present invention, but will of course be included among the characteristics of the cellulose product of the invention if to be employed according to such high-requirement standards.